Gene Therapy in the Cornea


Several advantages are apparent in making the cornea particularly attractive for gene transfer: it has a well‐defined anatomy and is easily accessible during ambulatory visits, as well as surgical procedures. The most important, and most difficult, challenge in gene therapy is the issue of delivery. Although naked or plasmid deoxyribonucleic acid (DNA) has occasionally been applied into the corneal stroma, usually, DNA is complexed in a vector to enhance delivery into the cornea. To date, the most efficient method for delivering nucleic acid‐based treatments mainly involves viral vectors, including retrovirus, lentivirus, adeno‐associated virus and adenovirus. However, nonviral vectors (lipid‐ or polymeric‐based systems), although less efficient, are safer and its production is simpler and cheaper than viral vectors. Corneal diseases potentially treatable by gene therapy include mucopolysaccharidosis VII, herpetic stromal keratitis, corneal neovascularisation, corneal burns and corneal transplantation and graft rejection, among others.

Key Concepts

  • The cornea is an ideal target for gene therapy as it is accessible, relatively immune privileged and easily monitored owing to its transparency.
  • The most important, and most difficult, challenge in corneal gene therapy is the issue of delivery.
  • Corneal diseases potentially treatable by gene therapy include mucopolysaccharidosis VII, herpetic stromal keratitis, corneal neovascularisation, corneal burns and corneal transplantation and graft rejection, among others.
  • Gene therapy in the cornea has been mainly studied in animal models, the clinical trials in humans being scarce.

Keywords: gene therapy; cornea; viral vectors; nonviral vectors; mucopolysaccharidosis VII; herpetic stromal keratitis; corneal neovascularisation; corneal scarring; corneal transplantation

Figure 1. Structure of the cornea.
Figure 2. Representative stereomicroscopy (a) and confocal microscopy (b) images showing transgene delivery in the rabbit stroma in vivo noted 2 days after topical application of transfection solution (1 µg μL−1 plasmid in 50 nmol DDAB and 50 nmol DOPE in 100 μL lactated Ringer's solution) onto the rabbit cornea via custom delivery technique. The plasmid expresses transgene under control of CMV + chicken‐β‐actin promoter. Nuclei are stained blue with DAPI. Reproduced from Mohan et al. () © Elsevier.
Figure 3. Barriers that DNA must overcome to reach the nucleus.
Figure 4. Onset and duration of AAV2/8 transgene expression. (a) Fluorescence detected by in vivo microscopy 3 days postinjection of AAV2/8. (b) At this timepoint, EGFP expression (arrow) was in the corneal epithelium (asterisk) as determined by histological epifluorescence studies. EGFP (arrows) could be detected in the stroma by 1 month postinjection by in vivo (c) and histological (d) studies. EGFP expression continued throughout the mouse cornea at 6 month postinjection in vivo (e) and by histological studies (f; montage of two overlapping photographs). EGFP expression persisted at 17 month postinjection (longest timepoint tested) as seen by in vivo (g) and histological studies (h). (i, j) Processing and analysis of the stack acquisition of the 10‐µm‐thick section shown in panel (h) using the Imaris software. Magnifications (a, c, e and g): 20×. Reproduced from Hippert et al. () © PLoS One (Creative Commons Attribution (CC BY) license).


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Rodríguez‐Gascón, Alicia, del Pozo‐Rodríguez, Ana, Isla, Arantxaxu, and Solinís, María A(Jun 2016) Gene Therapy in the Cornea. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024274]